PMID- 11447589
OWN - NLM
STAT- MEDLINE
DCOM- 20010830
LR  - 20190906
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 436
IP  - 4
DP  - 2001 Aug 6
TI  - Neurotrophism without neurotropism: BDNF promotes survival but not growth of 
      lesioned corticospinal neurons.
PG  - 456-70
AB  - Neurotrophic factors exert many effects on the intact and lesioned adult central 
      nervous system (CNS). Among these effects are prevention of neuronal death 
      (neurotrophism) and promotion of axonal growth (neurotropism) after injury. To 
      date, however, it has not been established whether survival and axonal growth 
      functions of neurotrophins can be independently modulated in injured adult 
      neurons in vivo. To address this question, the ability of brain-derived 
      neurotrophic factor (BDNF) to influence corticospinal motor neuronal survival and 
      axonal growth was examined in two injury paradigms. In the first paradigm, a 
      survival assay, adult Fischer 344 rats underwent subcortical lesions followed by 
      grafts to the lesion cavity of syngenic fibroblasts genetically modified to 
      secrete high amounts BDNF or, in control subjects, the reporter gene green 
      fluorescent protein. In control subjects, only 36.2 +/- 7.0% of the retrogradely 
      labeled corticospinal neurons survived the lesion, whereas 89.8 +/- 5.9% (P < 
      0.001) of the corticospinal neurons survived in animals that received 
      BDNF-secreting grafts. However, in an axonal growth assay, BDNF-secreting cell 
      grafts that were placed into either subcortical lesion sites or sites of thoracic 
      spinal cord injury failed to elicit corticospinal axonal growth. Despite this 
      lack of a neurotropic effect on lesioned corticospinal axons, BDNF-secreting cell 
      grafts placed in the injured spinal cord significantly augmented the growth of 
      other types of axons, including local motor, sensory, and coerulospinal axons. 
      Immunolabeling for tyrosine kinase B (trkB) demonstrated that BDNF receptors were 
      present on corticospinal neuronal somata and apical dendrites but were not 
      detected on their projecting axons. Thus, single classes of neurons in the adult 
      CNS appear to exhibit disparate survival and growth sensitivity to neurotrophic 
      factors, potentially attributable at least in part to differential trafficking of 
      neurotrophin receptors. The possibility of tropic/trophic divergence must be 
      considered when designing strategies to promote CNS recovery from injury.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Lu, P
AU  - Lu P
AD  - Department of Neurosciences, University of California, San Diego, La Jolla, 
      California 92093-0626, USA.
FAU - Blesch, A
AU  - Blesch A
FAU - Tuszynski, M H
AU  - Tuszynski MH
LA  - eng
GR  - NS 37083/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Comp Neurol
JT  - The Journal of comparative neurology
JID - 0406041
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/physiology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cell Transplantation
MH  - Cerebral Cortex/cytology/*physiology
MH  - Fibroblasts/metabolism/transplantation
MH  - Male
MH  - Neural Pathways/cytology/drug effects/growth & development
MH  - Neurons/*drug effects
MH  - Neurons, Afferent/drug effects
MH  - Phenotype
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptor, trkB/metabolism
MH  - Spinal Cord/cytology/*physiology
EDAT- 2001/07/12 10:00
MHDA- 2001/08/31 10:01
CRDT- 2001/07/12 10:00
PHST- 2001/07/12 10:00 [pubmed]
PHST- 2001/08/31 10:01 [medline]
PHST- 2001/07/12 10:00 [entrez]
AID - 10.1002/cne.1080 [doi]
PST - ppublish
SO  - J Comp Neurol. 2001 Aug 6;436(4):456-70. doi: 10.1002/cne.1080.